Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila
Abstract Sleep and circadian rhythm disruptions are frequent comorbidities of Parkinson’s disease (PD), a disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, the causal role of circadian clocks in the degenerative process remains uncertain. W...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41540-y |
| _version_ | 1797558486806036480 |
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| author | Michaëla Majcin Dorcikova Lou C. Duret Emma Pottié Emi Nagoshi |
| author_facet | Michaëla Majcin Dorcikova Lou C. Duret Emma Pottié Emi Nagoshi |
| author_sort | Michaëla Majcin Dorcikova |
| collection | DOAJ |
| description | Abstract Sleep and circadian rhythm disruptions are frequent comorbidities of Parkinson’s disease (PD), a disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, the causal role of circadian clocks in the degenerative process remains uncertain. We demonstrated here that circadian clocks regulate the rhythmicity and magnitude of the vulnerability of DA neurons to oxidative stress in male Drosophila. Circadian pacemaker neurons are presynaptic to a subset of DA neurons and rhythmically modulate their susceptibility to degeneration. The arrhythmic period (per) gene null mutation exacerbates the age-dependent loss of DA neurons and, in combination with brief oxidative stress, causes premature animal death. These findings suggest that circadian clock disruption promotes dopaminergic neurodegeneration. |
| first_indexed | 2024-03-10T17:32:06Z |
| format | Article |
| id | doaj.art-e4656673773a45b197e3f4d06aadadbb |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:32:06Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-e4656673773a45b197e3f4d06aadadbb2023-11-20T10:00:37ZengNature PortfolioNature Communications2041-17232023-09-0114111610.1038/s41467-023-41540-yCircadian clock disruption promotes the degeneration of dopaminergic neurons in male DrosophilaMichaëla Majcin Dorcikova0Lou C. Duret1Emma Pottié2Emi Nagoshi3Department of Genetics and Evolution and Institute of Genetics and Genomics of Geneva (iGE3), University of GenevaDepartment of Genetics and Evolution and Institute of Genetics and Genomics of Geneva (iGE3), University of GenevaDepartment of Genetics and Evolution and Institute of Genetics and Genomics of Geneva (iGE3), University of GenevaDepartment of Genetics and Evolution and Institute of Genetics and Genomics of Geneva (iGE3), University of GenevaAbstract Sleep and circadian rhythm disruptions are frequent comorbidities of Parkinson’s disease (PD), a disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, the causal role of circadian clocks in the degenerative process remains uncertain. We demonstrated here that circadian clocks regulate the rhythmicity and magnitude of the vulnerability of DA neurons to oxidative stress in male Drosophila. Circadian pacemaker neurons are presynaptic to a subset of DA neurons and rhythmically modulate their susceptibility to degeneration. The arrhythmic period (per) gene null mutation exacerbates the age-dependent loss of DA neurons and, in combination with brief oxidative stress, causes premature animal death. These findings suggest that circadian clock disruption promotes dopaminergic neurodegeneration.https://doi.org/10.1038/s41467-023-41540-y |
| spellingShingle | Michaëla Majcin Dorcikova Lou C. Duret Emma Pottié Emi Nagoshi Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila Nature Communications |
| title | Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila |
| title_full | Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila |
| title_fullStr | Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila |
| title_full_unstemmed | Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila |
| title_short | Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila |
| title_sort | circadian clock disruption promotes the degeneration of dopaminergic neurons in male drosophila |
| url | https://doi.org/10.1038/s41467-023-41540-y |
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